A new glucose-responsive formulation for self-regulated insulin delivery was constructed by packing insulin, glucose-specific enzymes into pH-sensitive polymersome-based nanovesicles assembled by a diblock copolymer. Glucose can passively transport across the bilayer membrane of the nanovesicle and be oxidized into gluconic acid by glucose oxidase, thereby causing a decrease in local pH. The acidic microenvironment causes the hydrolysis of the pH sensitive nanovesicle that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies validated that the release of insulin from nanovesicle was effectively correlated with the external glucose concentration. In vivo experiments, in which diabetic mice were subcutaneously administered with the nanovesicles, demonstrate that a single injection of the developed nanovesicle facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 5 days.

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This study described information about the preference of place of death and its potential predictive factors in terminally ill patients with cancer in mainland of China.

The coastal part of China and its surrounding regions are dominated by a highly dense population and highly developed economy. Extreme precipitation events (EPEs) cause a lot of damage and hence changes in these events and their causes have been drawing considerable attention. This study investigated EPEs resulting from western North Pacific (WNP) tropical cyclones (TCs) and their potential link to El Niño–Southern Oscillation (ENSO), using TC track data, daily precipitation data from 2313 stations for 1951–2014, and the NCAR–NCEP reanalysis dataset. Two types of EPEs were considered: EPEs within 500 km from the TC center, and those caused by mesoscale and synoptic systems, referred to as predecessor rain events (PREs), beyond 1000 km from the TC center. Results indicated significant impacts of TCs on EPEs along the coastal areas, and discernable effects in inland areas of China. However, the effect of TCs on EPEs tended to be modulated by ENSO. During neutral years, inland areas of China are more affected by TC-induced extreme precipitation than during El Niño or La Niña years, with the highest density of TC tracks and larger-than-average numbers of tropical storms, typhoons, and landfalling TCs. During the El Niño phase, the central and eastern equatorial Pacific was characterized by higher sea surface temperature (SST), greater low-level vorticity (1000 hPa) and upper-level divergence (250 hPa), and stronger prevailing westerlies, which combined to trigger the movement of mean genesis to the eastern and southeastern WNP, resulting in fewer TCs passing through the Chinese territory.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1(PVT1) was aberrantly expressed in various cancers and is associated with tumor prognosis. Here, we aim to investigate its function in prostate cancer. Small interfering RNA against PVT1 was transfected into prostate cancer cell lines and cell growth and apoptosis were analyzed. Our results showed that PVT1 was overexpressed in prostate cancer tissues and cells. Higher levels of PVT1 indicated poorer overall survival and disease-free survival. A significant association was found between PVT1 expression and tumor stage. Besides, PVT1 knockdown significantly inhibited prostate cancer growth in vivo and in vitro and promoted cell apoptosis. PVT1 knockdown also significantly upregulated the expression of cleaved caspase-3 and cleaved caspase-9, but downregulated the expression of c-Myc in prostate cancer cell lines. Our results suggest that PVT1 played an oncogenic role in prostate cancer and could be used as a potential biomarker for diagnosis of prostate cancer.

The integration of an injectable insulin‐encapsulated nano‐network with a focused ultrasound system (FUS) can remotely regulate insulin release both in vitro and in vivo. A single subcutaneous injection of the nano‐network with intermittent FUS administration facilitates reduction of the blood glucose levels in type 1 diabetic mice for up to 10 d.

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BackgroundAstaxanthin is a natural carotenoid pigment with tremendous antioxidant activity and great commercial value. Microbial production of astaxanthin via metabolic engineering has become a promising alternative. Although great efforts have been conducted by tuning the heterologous modules and precursor pools, the astaxanthin yields in these non-carotenogenic microorganisms were still unsatisfactory for commercialization, indicating that in addition to targeted tailoring limited targets guided by rationally metabolic design, combining more globe disturbances in astaxanthin biosynthesis system and uncovering new molecular mechanisms seem to be much more crucial for further development. Since combined metabolic engineering with mutagenesis by screening is a powerful tool to achieve more global variations and even uncover more molecular targets, this study would apply a comprehensive approach integrating heterologous module engineering and mutagenesis by atmospheric and room temperature plasma (ARTP) to promote astaxanthin production in Saccharomyces cerevisiae.ResultsHere, compared to the strain with β-carotene hydroxylase (CrtZ) from Alcaligenes sp. strain PC-1, involving new CrtZ from Agrobacterium aurantiacum enhanced astaxanthin yield to 1.78-fold and increased astaxanthin ratio to 88.7% (from 66.6%). Astaxanthin yield was further increased by 0.83-fold (to 10.1 mg/g DCW) via ARTP mutagenesis, which is the highest reported yield at shake-flask level in yeast so far. Three underlying molecular targets (CSS1, YBR012W-B and DAN4) associated with astaxanthin biosynthesis were first uncovered by comparative genomics analysis. To be noted, individual deletion of CSS1 can recover 75.6% improvement on astaxanthin yield achieved by ARTP mutagenesis, indicating CSS1 was a very promising molecular target for further development. Eventually, 217.9 mg/L astaxanthin (astaxanthin ratio was 89.4% and astaxanthin yield was up to 13.8 mg/g DCW) was obtained in 5-L fermenter without any addition of inducers.ConclusionsThrough integrating rational engineering of pathway modules and random mutagenesis of hosts efficiently, our report stepwise promoted astaxanthin yield to achieve the highest reported one in yeast so far. This work not only breaks the upper ceiling of astaxanthin production in yeast, but also fulfills the underlying molecular targets pools with regard to isoprenoid microbial overproductions.Electronic supplementary materialThe online version of this article (10.1186/s13068-018-1227-4) contains supplementary material, which is available to authorized users.